Importance of N-glycosylation positioning for cell-surface expression, targeting, affinity and quality control of the human AT1 receptor

Lanctot, Pascal M.; Leclerc, Patrice C.; Clement, M.G.; Auger‐Messier, Mannix; Escher, Emanuel; Leduc, Richard; Guillemette, Gaétan

doi:10.1042/bj20050189

Cited by 53 publications

(40 citation statements)

References 38 publications

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“…The increase in immunostaining bands observed in cortical tissues and BBMs was different in that the major band of increased expression was the 64-kDa band in BBM samples, whereas the lower nonglycosylated 42-kDa bands were increased in the cortical homogenates. Work by others has demonstrated that AT 1 receptors are glycosylated with a major glycosylated band migrating at ϳ64 kDa (11,33) and that glycosylation is important for the efficient movement of the receptor to the cell surface (5,11,16,17). Thus the predominance of a glycosylated form of the AT 1 receptor associated with the BBM is not surprising.…”

Section: Discussionmentioning

confidence: 97%

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Nagami

Chang²,

Plato³

et al. 2008

American Journal of Physiology-Renal Physiology

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Nagami GT, Chang JA, Plato ME, Santamaria R. Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II. Am J Physiol Renal Physiol 295: F1864 -F1870, 2008. First published October 22, 2008 doi:10.1152/ajprenal.90410.2008.-The proximal tubule defends the body against acid challenges by enhancing its production and secretion of ammonia. Our previous studies demonstrated an enhanced ammoniagenic response of the proximal tubule to ANG II added to the lumen in vitro after an in vivo acid challenge. The present study examined the effect of NH 4Cl acid loading in vivo on renal cortical type 1 ANG II (AT 1) receptor expression, the effect of low pH on AT 1 receptor expression in a proximal tubule cells in culture, and their response to ANG II. A short-term (18 h) NH 4Cl load in vivo resulted in increased renal cortical AT 1 receptor mRNA expression and increased brush-border membrane AT 1 receptor protein expression levels. Changing the cell culture pH from 7.4 to 7.0 for at least 2 h increased cell surface expression of AT 1 receptors and enhanced the stimulatory effect of ANG II on ammonia production rates. This increased ammoniagenic response to ANG II and the early enhancement of cell surface expression induced by exposure of the cultured proximal tubule cells to pH 7.0 were prevented by treatment with colchicine. These results suggest that, after acid challenges, the enhanced ammoniagenic response of the proximal tubule to ANG II is, in part, mediated by increased AT 1 receptor cell surface expression and that the enhancement of receptor expression plays an important role in the early response of the proximal tubule to acid challenges. ammoniagenesis; angiotensin type receptor; cell surface; acidosis; colchicine THE PROXIMAL TUBULE PLAYS an important role in defending the body against acid challenges by producing and secreting tNH 3 (tNH 3 ϭ NH 4 ϩ ϩ NH 3 ) (21). Renal tNH 3 production and excretion are enhanced in response to acid challenges (28, 30), and the major site of the increase in tNH 3 production and secretion rates that occur in response to acid challenges is the proximal tubule (21).ANG II plays an important role in the regulation of tNH 3 production by the proximal tubule (4,19,20,22). When tested in vitro, ANG II has concentration-dependent effects on tNH 3 production and transport by the proximal tubule (19,20). The stimulatory effect of ANG II on tNH 3 production rates is mediated by type 1 ANG II (AT 1 ) receptors, and this stimulatory effect is enhanced in proximal tubule segments derived from acid-loaded mice (22)(23)(24).Using in vitro microperfused mouse proximal tubules, we previously demonstrated that a short-term (18 h) NH 4 Cl acid challenge in vivo resulted in an increased stimulatory effect of ANG II on tNH 3 production (22). Nevertheless, it was unclear whether upregulation of the systemic renin-angiotensin system with acid loading (9, 10, 27) was responsible for the increased ammoniagenic response to ANG II of...

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Section: Discussionmentioning

confidence: 97%

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Nagami

Chang²,

Plato³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…In human RPT cells, Fen (1 μM for 20 min) decreased AT 1 R protein expression (Figure 2). The effect of Fen on AT 1 R protein expression was observed for the approximately 70-90 kDa band, but not for the approximately 40-60 kDa band; presumably, the former represents the glycosylated form of AT 1 R (17,18). The observed change in AT 1 R expression was specifically caused by D 1 -like receptor stimulation, because cotreatment with SCH23390, a D 1 -like receptor antagonist that had no effect by itself, abrogated the decrease in AT 1 R protein expression (Figure 2).…”

Section: Elevated Blood Pressure In Drd5 -/-Mice Is Normalized By An mentioning

confidence: 95%

“…Human bradykinin B2 receptor requires N-glycosylation for its maturation at the cell surface (44); certain sites of β 2 -adrenergic receptor N-glycosylation can alter receptor targeting to the degradation pathway (45). Both dopamine receptors (46,47) and the AT 1 R (17,18) are N-glycosylated. Glycosylation is required for the D 5 R to be functionally expressed at the cell surface (46).…”

Section: Discussionmentioning

confidence: 99%

“…Glycosylation is required for the D 5 R to be functionally expressed at the cell surface (46). N-glycosylation of the AT 1 R is important for its proper folding, targeting, and cell surface display (18). Our results showed that glycosylation was required for the interaction of AT 1 R with D 5 R ( Figure 7B), which is consistent with previous observation that glycosylation is important for their homologous (44) or heterologous (47) interaction with their binding partners to accomplish a series of intracellular functions.…”

Section: Discussionmentioning

confidence: 99%

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Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells

Li¹,

Armando²,

Yu³

et al. 2008

J. Clin. Invest.

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Hypertension is a multigenic disorder in which abnormal counterregulation between dopamine and (1-4). The D 5 R is widely expressed in the rodent kidney, specifically in the proximal and distal tubules, cortical collecting ducts, medullary ascending limbs of Henle, and arterioles, but not in the glomeruli, juxtaglomerular cells, or macula densa (5). The AT 1 R is also widely expressed in the kidney, specifically in the proximal and distal tubules, cortical

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“…Human AT 1 R-EGFP, or its empty vector pEGFP-N1, 25 was transfected into HEK293 cells using Lipofectamine ™ 2000 transfection reagents ͑Invitrogen͒, according to the manufacturer's instructions, as previously described. 26 …”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

2010

J. Biomed. Opt

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Abstract. The dynamic regulation of the cellular trafficking of human angiotensin ͑Ang͒ type 1 receptor ͑AT 1 R͒ is not well understood. Therefore, we investigated the cellular trafficking of AT 1 R-enhanced green fluorescent protein ͑EGFP͒ ͑AT 1 R-EGFP͒ heterologously expressed in HEK293 cells by determining the change in donor lifetime ͑AT 1 R-EGFP͒ in the presence or absence of acceptor͑s͒ using fluorescence lifetime imaging-fluorescence resonance energy transfer ͑FRET͒ microscopy. The average lifetime of AT 1 R-EGFP in our donor-alone samples was ϳ2.33 ns. The basal state lifetime was shortened slightly in the presence of Rab5 ͑2.01± 0.10 ns͒ or Rab7 ͑2.11± 0.11 ns͒ labeled with Alexa 555, as the acceptor fluorophore. A 5-min Ang II treatment markedly shortened the lifetime of AT 1 R-EGFP in the presence of Rab5-Alexa 555 ͑1.78± 0.31 ns͒ but was affected minimally in the presence of Rab7-Alexa 555 ͑2.09± 0.37 ns͒. A 30-min Ang II treatment further decreased the AT 1 R-EGFP lifetime in the presence of both Rab5-and Rab7-Alexa 555. Latrunculin A but not nocodazole pretreatment blocked the ability of Ang II to shorten the AT 1 R-EGFP lifetime. The occurrence of FRET between AT 1 R-EGFP ͑donor͒ and LAMP1-Alexa 555 ͑acceptor͒ with Ang II stimulation was impaired by photobleaching the acceptor. These studies demonstrate that Ang IIinduced AT 1 R lysosomal degradation through its association with LAMP1 is regulated by Rab5/7 via mechanisms that are dependent on intact actin cytoskeletons.

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Importance of N-glycosylation positioning for cell-surface expression, targeting, affinity and quality control of the human AT1 receptor

Cited by 53 publications

References 38 publications

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells

Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

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